Application of NMR Spectroscopy and Mass Spectrometry to the Structural Elucidation of Modified Flavan‐3‐ols and Their Coupling Reaction Products*

NMR and MS techniques were used for the unambiguous structural elucidation of synthesized modified monomeric and dimeric flavan‐3‐ols presenting different substituents on the A‐ring C8 position. The full characterization of the synthesized compounds was achieved by concerted use of NMR and ESI‐MS techniques. Assignments of proton and carbon atoms was achieved through analysis of the 1D ¹H and ¹³C NMR spectra combined with homo‐ and heteronuclear 2D NMR experiments. In each case, HMBC correlation between proton H2 and carbon C8a was observed allowing assignment of this carbon, which represents the key for attribution of the A‐ring carbon atoms. The synthesis and structural characterization of activated monomeric and dimeric flavanols were also achieved and used as precursors for preparation of natural and modified dimeric procyanidin derivatives. The preparation of various dimeric species involving modified flavanols was explored through different coupling reactions. The structures of the compounds formed were characterized on the basis of their MS and NMR spectral analysis. Dimeric species were characterized through proton–proton and proton–carbon correlations, which distinguished between the different flavanol moieties and established their sequences.     

Structural Assignment of Isomeric S‐ and S,N‐1‐Alkoxycarbonylalkylated 6‐Amino‐2‐thiouracil Derivatives by Means of 1H and 13C NMR Spectroscopy

Abstract

The structures of new isomeric 2‐alkoxycarbonylalkylthio‐ and 2‐alkoxy‐ carbonylalkylthio‐1‐alkoxycarbonylalkyl‐6‐aminouracils (1–21) have been established on the basis of the ¹H NMR and ¹³C NMR spectroscopic data. The ¹H NMR and ¹³C NMR spectra of 1–21 have been fully assigned by a combination of two‐dimensional experiments [heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond correlation (HMBC)]. The ¹³C NMR spectra have been shown to be able to differentiate between isomers.     

Structural Assignment of Stilbenethiols and Chalconethiols and Differentiation of Their Isomeric Derivatives by Means of 1H‐ and 13C‐NMR Spectroscopy

Abstract

The ¹H‐ and ¹³C‐NMR spectra of some substituted stilbenes and chalcones were assigned unambiguously on the basis of a combination of homo‐ (COSY) and heteronuclear (HETCOR) two‐dimensional methods, the chemical shifts, as well as spin‐coupling constants. The A_ik empirical parameters of the –O–C(S)–N(CH₃)₂, –S–C(O)–N(CH₃)₂, and –SH group were calculated to help predict the chemical shifts of substituted stilbenes, 4′‐nitrostilbenes, and chalcones. The ¹H‐ and ¹³C‐NMR spectra have been shown to be able to differentiate between the isomers of O‐stilbenyl (4, 5) and S‐stilbenyl N,N‐dimethylthiocarbamates (7, 8) as well as O‐chalconyl (6) and S‐chalconyl N,N‐dimethylthiocarbamates (9).     

Structural Assignments of 1‐(β‐d‐Glucopyranosyl)‐1,2,3‐triazoles by 1H‐ and 13C‐NMR Study

The ¹H‐ and ¹³C‐NMR spectra of 1‐β‐d‐glucopyranosyl‐1,2,3‐triazole‐4,5‐dimethyl carboxylate, 1‐β‐d‐glucopyranosyl‐1,2,3‐triazole‐4,5‐dicarboxamide, ‐dialkylcarboxamide‐N‐nucleosides 4–18, and 6‐amino‐4H‐1‐(1‐β‐d‐glucopyranosyl)‐8‐hydroxy‐1,2,3‐triazolo[4,5‐e][1,3]‐diazepin‐4‐one 19 had been studied. Resonance signals and anomeric configurations were assigned by homo‐ and heteronuclear two dimensional methods (DQF‐COSY, HSQC, HMBC, HMQC, ROESY).     

Kinetics of 1H→13C NMR cross-polarization in polymorphs and solvates of the antipsychotic drug olanzapine

The (1)H→(13)C NMR cross-polarization (CP) was studied under magic-angle spinning at 7.5 kHz in various crystal forms of the antipsychotic drug olanzapine: two polymorphs (metastable I and stable II) and eight solvates containing organic solvent and water molecules. The CP kinetics followed the non-classical I-I(*)-S model, in which CP begins in a spin cluster of proximate abundant spins I(*) and rare spins S, then is controlled by spin diffusion of the abundant spins I from bulk to the I(*) spins of the spin cluster and finally is governed by spin-lattice relaxation of the abundant spins in the rotating frame. The corresponding CP kinetics parameters were determined and analyzed. It was demonstrated that the, λ and T(df) values (the CP time constant, the cluster composition parameter and the (1)H spin-diffusion constant, respectively) were very useful to discriminate the functional groups, especially in the 3D parameter space. In order to conveniently analyze the large amount (175) of the collected CP parameters, the number of the observed variables was reduced using the principal component (PC) analysis. The 2D plot of PC2 vs. PC1 showed adequate separation of the CH(3), CH(2), CH and C cases (C stands for carbons without adjacent hydrogens). It was demonstrated that those cases were located along the PC1 axis in the order of increasing (1)H-(13)C dipolar couplings: C相似文献   

1H–13C hetero-nuclear dipole–dipole couplings of methyl groups in stationary and magic angle spinning solid-state NMR experiments of peptides and proteins

¹³C NMR of isotopically labeled methyl groups has the potential to combine spectroscopic simplicity with ease of labeling for protein NMR studies. However, in most high resolution separated local field experiments, such as polarization inversion spin exchange at the magic angle (PISEMA), that are used to measure ¹H–¹³C hetero-nuclear dipolar couplings, the four-spin system of the methyl group presents complications. In this study, the properties of the ¹H–¹³C hetero-nuclear dipolar interactions of ¹³C-labeled methyl groups are revealed through solid-state NMR experiments on a range of samples, including single crystals, stationary powders, and magic angle spinning of powders, of ¹³C₃ labeled alanine alone and incorporated into a protein. The spectral simplifications resulting from proton detected local field (PDLF) experiments are shown to enhance resolution and simplify the interpretation of results on single crystals, magnetically aligned samples, and powders. The complementarity of stationary sample and magic angle spinning (MAS) measurements of dipolar couplings is demonstrated by applying polarization inversion spin exchange at the magic angle and magic angle spinning (PISEMAMAS) to unoriented samples.     

The partial 1H NMR spectra of Al–OH and molecular H2O in hydrous aluminosilicate glasses: Component-Resolved analysis of 27Al–1H cross polarization and 1H spin-echo MAS NMR spectra

The Component-Resolved methodology was applied to ¹H spin-echo and ²⁷Al–¹H cross polarization (CP) MAS NMR data of aluminosilicate glasses. The method was able to resolve two components with different T2 relaxation rates, hydroxyl groups (OH) and molecular water (H₂O_mol), from the spin-echo data and to determine partial spectra and the relative abundances of OH and H₂O_mol. The algorithm resolved two to three components with different ²⁷Al–¹H CP dynamics from the ²⁷Al–¹H cross polarization data; the obtained partial NMR spectra for Al–OH are in excellent agreement with those obtained previously from the difference spectra between spectra with various contact times and confirm previous quantitative results and models for the Al–OH, Si–OH and H₂O_mol speciation (Malfait and Xue, 2010).     

Quantitative Measurement of Transverse and Longitudinal Cross-Correlation between13C–1H Dipolar Interaction and13C Chemical Shift Anisotropy: Application to a13C-Labeled DNA Duplex

Measurement of both longitudinal and transverse relaxation interference (cross-correlation) between¹³C chemical shift anisotropy and¹³C–¹H dipolar interactions is described. The ratio of the transverse to longitudinal cross-correlation rates readily yields the ratio of spectral densitiesJ(0)/J(ω_C), independent of any structural attributes such as internuclear distance or chemical shift tensor. The spectral density at zero frequencyJ(0) is also independent of chemical exchange effects. With limited internal motions, the ratio also enables an accurate evaluation of the correlation time for overall molecular tumbling. Applicability of this approach to investigating dynamics has been demonstrated by measurements made at three temperatures using a DNA decamer duplex with purines randomly enriched to 15% in¹³C.     

Assignments of the 13C NMR Spectra of Enhydrin and 2′,3′-Dehydromelnerin A and the Molecular Structure of Enhydrin

Abstract

Two melampolide-type sesquiterpene lactones, enhydrin and 2,′ 3′-dehydromelnerin A, were isolated from a Louisiana population of Polymnia uvedalia. Their ¹³C NMR spectra were assigned using ¹³C-¹H correlation, DEPT and COLOC experiments. The molecular structure of enhydrin was established by single crystal X-ray diffraction.     

High-resolution infrared spectroscopy of H12C13CD and H13C12CD in the 470–5200 cm−1 spectral region

The fundamental ro-vibrational bands and the 2ν₄?←?GS, 2ν₅?←?GS, 2ν₃?←?GS, ν₄?+?ν₅?←?GS, ν₃?+?ν₄?←?GS, ν₃?+?ν₄?←?ν?₄, ν₃?+?ν₅?←?ν₅, overtone, combination and hot bands of the two rare isotopologues of acetylene H¹²C¹³CD and H¹³C¹²CD have been detected by Fourier transform infrared spectroscopy (FTIR). The analysis of the data has provided very accurate rotational and vibrational parameters for the ground and for the vibrationally excited states.     

1H, 13C and 15N NMR Studies of Protonation in Imidazo[1,2-α]Pyrimidine and Derivatives

We have studied1 the protonation behaviour of several cardiotonic polyazaheterocycles and recently shown that the 2-arylimidazo[l,2-a]pyrimidine (3a) undergoes protonation at the imidazo nitrogen (Nl). These investigations have utilised the shielding of acarbon nuclei and increases in ¹³C-¹H or ¹H-¹H couplings that occur on protonation of a heterocyclic nitrogen. We now report unequivocal protonation studies of the parent heterocycle, imidazo[1,2-a]pyrimidine (l), and its 2-aryl derivative (3b) which have allowed the effect of 2-aryl substitution on protonation to be determined. ¹⁵N NMR spectroscopy was employed to determine the protonation site of (1) in a titration study with H2SO4. In addition the N-methyl quaternary salts (21, (4) and (5) were prepared and ¹⁵N, ¹³C and ¹H chemical shifts measured so as to provide unambiguous substituent effects uncomplicated by possible proton transfers.     

Fundamental and combination bands of CO2–C2H2 and CO2–C2D2 in the mid-infrared region

Spectra of the weakly bound CO₂–C₂H₂ and CO₂–C₂D₂ complexes are observed in the regions of CO₂ ν₃ (≈ 2349 cm^?1) and C₂D₂ ν₃ (≈ 2440 cm^?1) fundamental vibrations, using an infrared optical parametric oscillator to probe a pulsed supersonic slit-jet expansion. Five bands are measured and analysed: the fundamental asymmetric stretch of the C₂D₂ component, two combination bands involving the out-of-plane torsional vibrations (C₂D₂ ν₃ + torsion and CO₂ ν₃ + torsion) for CO₂–C₂D₂, and two combination bands involving an intermolecular in-plane bending vibration for CO₂–C₂H₂ and CO₂–C₂D₂. The resulting intermolecular frequencies are 61.408(1), 54.5(5), 39.9(5), and 39.961(1) cm^?1 for CO₂–C₂H₂ and CO₂–C₂D₂ in-plane vibrations, and CO₂–C₂D₂ out-of-plane torsional vibrations in CO₂ and C₂D₂ regions, respectively. This is the first experimental determination of these intermolecular vibrational frequencies.     

The 2CH excitation band in C2H2–N2O and 2CH+torsion combination bands in C2H2–N2O and C2H2–CO2

A preliminary analysis of the 2CH excitation band in C₂H₂–N₂O in the 1.5 µm range (K. Didriche, C. Lauzin, P. Macko, M. Herman and W.J. Lafferty, Chem. Phys. Letters 469, 35 (2009).), only considering 117 low J-, and K_a - vibration-rotation lines, is significantly extended thanks to the analysis of new spectra including very regular series of lines with J/K_a up to 31/15. 1271 b-type lines were assigned. Perturbations are briefly discussed. The rotational temperature in the experiments is estimated to be 20?K and the upper state mean half-time is 1.6?ns for non perturbed levels. The previous analyses of the 2CH + torsion band in C₂H₂–N₂O and in C₂H₂–CO₂ (C. Lauzin, K. Didriche, T. Földes and M. Herman, Mol. Phys. 109, 2105 (2011).), are also extended to include 286 and 234 lines, respectively, also correcting for calibration errors. New rotational constants are obtained using a rigid rotor Hamiltonian by simultaneously fitting the ground, 2CH and 2CH + torsion states in C₂H₂–N₂O, and the latter state, only, in C₂H₂–CO₂.     

Selective detection of single-enantiomer spectrum of chiral molecules aligned in the polypeptide liquid crystalline solvent: Transition selective one-dimensional 1H–1H COSY

One-dimensional (1D) proton NMR spectra of enantiomers are generally undecipherable in chiral orienting poly-γ-benzyl-l-glutamate (PBLG)/CDCl₃ solvent. This arises due to large number of couplings, in addition to superposition of spectra from both the enantiomers, severely hindering the ¹H detection. On the other hand in the present study the benefit is derived from the presence of several couplings among the entire network of interacting protons. Transition selective 1D ¹H–¹H correlation experiment (1D-COSY) which utilizes the coupling assisted transfer of magnetization not only for unraveling the overlap but also for the selective detection of enantiopure spectrum is reported. The experiment is simple, easy to implement and provides accurate eanantiomeric excess in addition to the determination of the proton–proton couplings of an enantiomer within a short experimental time (few minutes).     

In situ 1H NMR Study of Nanoreactor Interaction NH3–H2O in Zeolite Nanopores

The interaction between ammonium NH₃ and H₂O molecules in zeolitic nanopores is studied by in situ ¹H nuclear magnetic resonance (NMR) method. The powder and single crystal samples of natural zeolites, heulandites Ca₄[Al₈Si₂₈O₇₂]·24H₂O and clinoptilolite (Na, K,Ca_1/2)₆[Al₆Si₃₀O₇₂], were used as the model system. It is shown that penetration of NH₃ into the zeolitic nanopores is accompanied by disordering of the hydrogen sublattice of zeolitic water and by the fast proton exchange NH₃ + H₂O ? [NH₄]⁺ + [OH]^? characterized by correlation frequency v _c = ~40 kHz. Another nanoreactor interactions are represented by interaction of [NH₄]⁺ ions with exchangeable Na⁺ and Ca²⁺ ions of the zeolitic structure. The slow ionic exchange [NH₄]⁺ → [Na,Ca_1/2]⁺ and binding of [NH₄]⁺ in cationic sites of the framework were visualized by NMR spectroscopy along with stepwise release of (Na,Ca_1/2)OH from zeolitic pores to the external surface of zeolite grains.     

Isotope Effects by Comparing 1H‐ and 2D‐NMR Spectra of 9,9′‐Bisbicyclo[4.3.0]‐cyclonona‐2,4,7‐triene

Abstract

Inverse secondary kinetic isotope effects are determined for the dimerization of all‐cis‐cyclononatetraenyl radical, 1, to its corresponding dimer, all‐cis‐9,9′‐bicyclonona‐1,3,5,7‐tetraene, 2, (step 1, k _H/k _D=0.5), and cyclization of the latter to 9,9′‐bisbicyclo[4.3.0]cyclonona‐2,4,7‐triene, 3 (step 2, k _H/k _D=0.75). These results are obtained by comparison of ¹H‐ and ²D‐NMR spectra of 3 and employment of a simple statistical method for acquiring kinetic data. This new strategy appears superior to conventional methods in being fast, simple, and less expensive.     

Direct Detection of Al–O–Al Structure in Aluminosilicate Specimens: A Use of Homo-Nuclear DQMAS NMR

A general strategy of Al–O–Al structure in various aluminosilicate was evaluated by combining triple-quantum magic angle spinning (3QMAS) and double-quantum homo-nuclear correlation under magic angle spinning (DQMAS) solid-state nuclear magnetic resonance (NMR) measurements with the aid of high magnetic field NMR (800 MHz for ¹H Larmor frequency). The results show that in many cases the direct detection of Al–O–Al sites in aluminosilicate crystals and glasses is possible; hence the extent of aluminum avoidance can be directly elucidated. Specifically, experimental evidence of Al–O–Al linkages in several aluminosilicate materials with Si/Al >1 was straightforwardly confirmed; and the existence of Al–O–Al is considered to have little correlation with the Si/Al ratio, but it may be strongly related to the cation and local structural arrangement. In addition, the presence of tri-clusters of (Si, Al)O₄-tetrahedra in aluminosilicate framework was proposed, which was thought to act as nuclei for formation and incorporation of cations to achieve charge neutrality.     

1H–13C–29Si triple resonance and REDOR solid-state NMR—A tool to study interactions between biosilica and organic molecules in diatom cell walls

Triple resonance solid-state NMR experiments using the spin combination ¹H–¹³C–²⁹Si are still rarely found in the literature. This is due to the low natural abundance of the two heteronuclei. Such experiments are, however, increasingly important to study hybrid materials such as biosilica and others. A suitable model substance, ideally labeled with both ¹³C and ²⁹Si, is thus very useful to optimize the experiments before applying them to studies of more complex samples such as biosilica. Tetraphenoxysilane could be synthesized in an easy, two-step synthesis including double isotope labelling. Using tetraphenoxysilane, we established a ¹H–¹³C–²⁹Si double CP-based HETCOR experiment and applied it to diatom biosilica from the diatom species Thalassiosira pseudonana. Furthermore, we carried out ¹H–¹³C{²⁹Si} CP-REDOR experiments in order to estimate the distance between the organic matrix and the biosilica. Our experiments on diatom biosilica strongly indicate a close contact between polyamine-containing parts of the organic matrix and the silica. This corroborates the assumption that the organic matrix is essential for the control of the cell wall formation.     

Recent Applications of Molecular Spectroscopy in Bioorganometallic Chemistry–Part 2: Ferrocenes and Other Organometallic Complexes

Abstract: This is the second part of an overview of the applications of the various molecular spectroscopic methods that have been employed in bioorganometallic chemistry research since 2005 focusing on ferrocenes and other non-metal carbonyl organometallic complexes. These spectroscopic methods encompass infrared (IR), nuclear magnetic resonance (NMR), mass, Raman, ultraviolet-visible (UV-Vis), and several other less common spectroscopic techniques.     

Mono and bidimensional1H NMR and inverse detected13C NMR of the duplex d(CA)3·d(TG)3

The unambiguous assignment of the aromatic protons of the duplex d(CA)₃·d(TG)₃ was carried out with the aid of HMQC and HMBC inverse detected¹³C NMR experiments atT=278 K. The NOE connections of these protons with the imino protons of the complementary bases — established by 2D NOESY experiments — indicated that the duplex is characterized by a canonical Watson-Crick basepairing pattern. Monodimensional¹H NMR experiments, also carried out atT=278K, in the presence of varying amounts of NaCl and with water suppression by presaturation and by spin echo techniques, showed that the imino protons of the TA and CG pairs of the duplex exchange with water through a process of local base pair opening and with different exchange rates.